The objective of the present project is to identify ras mutants which have the ability to suppress cellular transformation. Point mutations of the v-H-ras oncogene at the codon for amino acid position 116 (asparagine to tyrosine, isoleucine and lysine) caused mutant p2ls to loss GTP-binding and transforming activities. Moreover, these mutants induced flat revertants when introduced into NIH3T3 cells transformed by an LTR-linked c-H-ras protooncogene. High level expression of mutant p2l was detected in these cells. These ras mutants also caused morphological reversion of NIH3T3 cells transformed by v-src, v-fms, v-sis and v-fes oncogenes. Microinjection of a neutralizing ras antibody revealed similar results. Most likely, these mutant p2ls inhibited the function of c-ras activities. These trans-dominant suppressor ras mutants will be very valuable for analysis of ras function. Experiments are in progress to investigate the relationship between ras and signaling pathways of cellular transformation.